title: A nutrigenomic framework to identify time-resolving responses of hepatic genes in diet-induced obese mice.
abstract: Obesity and its related complications have emerged as global health problems; however, the pathophysiological mechanism of obesity is still not fully understood. In this study, C57BL/6J mice were fed a normal (ND) or high-fat diet (HFD) for 0, 2, 4, 6, 8, 12, 20, and 24 weeks and the time course was systemically analyzed specifically for the hepatic transcriptome profile. Genes that were differentially expressed in the HFD-fed mice were clustered into 49 clusters and further classified into 8 different expression patterns: long-term up-regulated (pattern 1), long-term downregulated (pattern 2), early up-regulated (pattern 3), early down-regulated (pattern 4), late up-regulated (pattern 5), late down-regulated (pattern 6), early up-regulated and late down-regulated (pattern 7), and early down-regulated and late up-regulated (pattern 8) HFD-responsive genes. Within each pattern, genes related with inflammation, insulin resistance, and lipid metabolism were extracted, and then, a protein-protein interaction network was generated. The pattern specific sub-network was as follows: pattern 1, cellular assembly and organization, and immunological disease, pattern 2, lipid metabolism, pattern 3, gene expression and inflammatory response, pattern 4, cell signaling, pattern 5, lipid metabolism, molecular transport, and small molecule biochemistry, pattern 6, protein synthesis and cell-to cell signaling and interaction and pattern 7, cell-to cell signaling, cellular growth and proliferation, and cell death. For pattern 8, no significant sub-networks were identified. Taken together, this suggests that genes involved in regulating gene expression and inflammatory response are up-regulated whereas genes involved in lipid metabolism and protein synthesis are down-regulated during diet-induced obesity development.
authors.affiliation: Green Bio Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 305-806, Korea.
authors.forename: Hyoung-Sam
authors.initials: HS
authors.lastname: Heo
authors.forename: Eunjung
authors.initials: E
authors.lastname: Kim
authors.forename: Seon-Min
authors.initials: SM
authors.lastname: Jeon
authors.forename: Eun-Young
authors.initials: EY
authors.lastname: Kwon
authors.forename: Su-Kyung
authors.initials: SK
authors.lastname: Shin
authors.forename: Hyojung
authors.initials: H
authors.lastname: Paik
authors.forename: Cheol-Goo
authors.initials: CG
authors.lastname: Hur
authors.forename: Myung-Sook
authors.initials: MS
authors.lastname: Choi
mesh_terms: D000818:Animals; D016000:Cluster Analysis; D059305:Diet, High-Fat; D015536:Down-Regulation / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks / Q000235:genetics; D007249:Inflammation / Q000235:genetics; D007333:Insulin Resistance / Q000235:genetics; D050356:Lipid Metabolism / Q000235:genetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D005810:Multigene Family; D054647:Nutrigenomics; D009765:Obesity / Q000235:genetics* / Q000473:pathology; D060066:Protein Interaction Maps / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D015854:Up-Regulation / Q000235:genetics
chemical_list: D012333:RNA, Messenger